title: Immune monitoring of anti cytomegalovirus antibodies and risk of cytomegalovirus disease in heart transplantation.
abstract: We sought to determine whether quantitative assessment of anti-cytomegalovirus (CMV) antibodies could be useful to identify patients at risk of cytomegalovirus (CMV) disease after heart transplantation (HT). 75 patients who underwent HT at a single health care center were prospectively studied. Induction therapy included 2 doses of daclizumab and maintenance tacrolimus (n=42) or cyclosporine (n=29), mycophenolate mofetil and prednisone. All patients received prophylaxis with gancyclovir or valganciclovir. Anti-CMV intravenous immunoglobulin (CMV-IG) was added in high risk patients (CMV D+/R- serostatus). Serial determinations of anti-CMV antibodies, immunoglobulins (IgG, IgA, IgM) and IgG-subclasses were analysed. CMV infection was based on detection of the virus by antigenemia. CMV disease consisted of detection of signs or symptoms attributable to this microorganism. Ten patients (13.3%) developed CMV disease. Mean time of development of CMV disease was 3.4+/-1.6 months. In Cox regression analysis, patients with low baseline anti-CMV titers (<4.26 natural logarithm of titer, RH: 8.1, 95%CI: 1.93-34.1, p=0.004) and recipients with 1-month post-HT IgG hypogammaglobulinemia (IgG<500 mg/dl, RH: 4.49, 95%CI: 1.26-15.94, p=0.02) were at higher risk of having CMV disease. Despite use of prophylactic CMV-IG, D+/R- patients showed significantly lower titers of anti-CMV antibodies at 7 d, 30 d and 90 d post HT as compared with HT recipients without infections. Four out of 6 of these patients developed late CMV disease. Monitoring of specific anti-CMV antibodies on the bedside warrants further evaluation as a potential tool to identify heart transplant recipients at higher risk of CMV disease.
authors.affiliation: Transplant Immunology Group, Immunology Department, University Hospital Gregorio Marañon, Madrid, Spain. esarmiento.hgugm@salud.madrid.org
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sarmiento
authors.forename: Nallibe
authors.initials: N
authors.lastname: Lanio
authors.forename: Antonio
authors.initials: A
authors.lastname: Gallego
authors.forename: Juan
authors.initials: J
authors.lastname: Rodriguez-Molina
authors.forename: Joaquin
authors.initials: J
authors.lastname: Navarro
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Yañez
authors.forename: Jesus
authors.initials: J
authors.lastname: Palomo
authors.forename: Cesar
authors.initials: C
authors.lastname: Rodríguez-Hernández
authors.forename: Manuel
authors.initials: M
authors.lastname: Ruiz
authors.forename: Roberto
authors.initials: R
authors.lastname: Alonso
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandez-Cruz
authors.forename: Javier
authors.initials: J
authors.lastname: Carbone
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012044:Regression Analysis
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous